One of the major goals of the effort to characterize the human genome is the production of high density genetic linkage maps of model species such as the mouse. Our mapping efforts rely on two different approaches. Traditionally we have used Chinese hamster x mouse somatic cell hybrids to assign newly identified genes to specific chromosomes. These hybrids continue to be useful to determine the number of genes identified by hybridization probes with multiple genomic copies, like the heat shock proteins genes, or to map genes which govern species specific traits expressed in tissue culture like the accessory factor for interferon gamma receptor. More recently, we have been mapping genes using Southern blot analysis of the progeny of two genetic crosses, an interspecies and an intersubspecies backcross. DNAs from the progeny of these crosses have been typed for a variety of polymorphic reference loci to permit mapping of unknown markers to specific positions on the linkage map. These studies have resulted in the chromosomal mapping of a large number of genes including the various genes expressed in nervous tissue, calcium channel genes, the mouse homolog of the cystic fibrosis transmembrane conductance regulator gene, and various genes for transcriptional factors. Several of these genes map at or near known mouse mutations and therefore are potential candidates for these mutations. Thus, one gene specifically expressed in melanocytes was mapped near the silver locus on chromosome 10, and another gene specifically expressed in brain was mapped near the coloboma neurological mutation and shown to be deleted in mutant coloboma mice.